A Study to Evaluate the Pharmacokinetics of BAL8728 After a Single Dose of Pyridinylmethyl-14C-Labeled Isavuconazonium Sulfate in Healthy Male Subjects

Healthy Subjects Clinical Trial

Official title:

A Phase 1 Open-Label Mass Balance Study to Evaluate the Pharmacokinetics of BAL8728 After A Single Intravenous Dose of 14C-Labeled Isavuconazonium Sulfate in Healthy Male Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02059590
• Other study ID #: 9766-CL-0050
• Status: Completed
• Phase: Phase 1
• First received: February 7, 2014
• Last updated: February 7, 2014
• Start date: April 2013
• Est. completion date: April 2013

Study information

• Verified date: February 2014
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the pharmacokinetics of 14C-labeled cleavage product (BAL8728), in particular the routes of excretion and extent ot metabolism of the cleavage product following administration of a single intravenous dose of pyridinylmethyl-14C-labeled prodrug isavuconazonium sulfate (BAL8557). In addition, identify the metabolic profile of BAL8728 in human plasma, urine and/or feces after a single intravenous dose of pyridinylmethyl-14C-labeled BAL8557 and evaluate the pharmacokinetics of BAL8728 and BAL4815. Safety and tolerability after a single intravenous dose of pyridinylmethyl-14C-labeled isavuconazonium sulfate will also be evaluated.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: April 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• The subject has a body weight of at least 45 kg and a body mass index of 18 to 32 kg/m2, inclusive.

• The subject's 12-lead electrocardiogram (ECG) is normal at Screening and Day -1; or, if abnormal, the abnormality is not clinically significant. The ECG for the subject has a QTcF of at least 360 but not more than 430 msec.

Exclusion Criteria:

• The subject has any clinically significant disease history of the following systems:

pulmonary, gastrointestinal, cardiovascular (including a history of clinically significant arrhythmia), hepatic, neurological, psychiatric, renal, genitourinary, endocrine, metabolic, dermatologic, immunologic, hematologic, or malignancy excluding non melanoma skin cancer.

• The subject has a positive test for hepatitis B surface antigen or hepatitis C antibodies at Screening or is known to be positive for human immunodeficiency virus.

• The subject has a known or suspected allergy to any of the azole class of compounds, or a history of multiple and/or severe allergies to drugs or foods or a history of severe anaphylactic reactions.

• The subject has used tobacco or nicotine containing products in the last 6 months prior to Day -1.

• The subject has had treatment with prescription drugs, over-the-counter medication, or complementary and alternative medicines within 14 days prior to Day -1, with the exception of occasional use of acetaminophen up to 2 g/day.

• The subject has participated in any interventional clinical study or has received any investigational agent within 28 days or 5 half-lives, whichever is longer, prior to Screening.

• The subject has had any significant blood loss, donated one unit (450 mL) of blood or more, or received a transfusion of any blood or blood products within 60 days or donated plasma within 7 days prior to clinic admission on Day -1.

Study Design

Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Healthy Subjects
• Pharmacokinetics of 14C-labeled Isavuconazonium Sulfate

Intervention

Drug:
• Pyridinylmethyl-14C-labeled isavuconazonium sulfate
Intravenous

Locations

Country	Name	City	State
United States	Covance	Madison	Wisconsin

Sponsors (2)

Lead Sponsor	Collaborator
Astellas Pharma Global Development, Inc.	Basilea Pharmaceutica International Ltd

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Radioactivity in whole blood and in plasma: Area under the concentration-time curve (AUC) from time of dosing to infinity (AUCinf)		20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9	No
Primary	Radioactivity in whole blood and in plasma: AUC from time of dosing to the last quantifiable concentration (AUClast)		20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9	No
Primary	Radioactivity in whole blood and in plasma: Maximum concentration (Cmax)		20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9	No
Primary	Radioactivity in whole blood and in plasma: Time to Attain Cmax (tmax)		20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9	No
Primary	Radioactivity in whole blood and in plasma: Apparent terminal elimination half-life (t1/2)		20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9	No
Primary	Radioactivity in emesis (if applicable)		After study drug administration up to Day 9	No
Primary	Radioactivity ratio blood/plasma		Day 1	No
Primary	Percent of dose and cumulative percent of dose of radioactivity recovered in urine		7 time intervals up to Day 4. If Day 4 is not the end of the study, sample collection will continue in 24 hour intervals until discharge up to Day 9	No
Primary	Percent of dose and cumulative percent dose of radioactivity recovered in feces		4 time intervals up to Day 4. If Day 4 is not the end of the study, sample collection will continue in 24 hour intervals until discharge up to Day 9	No
Primary	Pharmacokinetics of BAL8728 (cleavage product) in plasma: AUCinf		20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9	No
Primary	Pharmacokinetics of BAL8728 (cleavage product) in plasma: AUClast		20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9	No
Primary	Pharmacokinetics of BAL8728 (cleavage product) in plasma: Cmax		20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9	No
Primary	Pharmacokinetics of BAL8728 (cleavage product) in plasma: tmax		20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9	No
Primary	Pharmacokinetics of BAL8728 (cleavage product) in plasma: total body clearance after intravenous dosing (CLtot)		20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9	No
Primary	Pharmacokinetics of BAL8728 (cleavage product) in plasma: volume of distribution during terminal phase after intravenous dosing (Vz)		20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9	No
Primary	Pharmacokinetics of BAL8728 (cleavage product) in plasma: t 1/2		20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9	No
Primary	Pharmacokinetics of BAL8728 (cleavage product) in urine: amount excreted (Ae)		7 time intervals up to Day 4. If Day 4 is not the end of the study, sample collection will continue in 24 hour intervals until discharge up to Day 9	No
Primary	Pharmacokinetics of BAL8728 (cleavage product) in urine: percent of unchanged drug excreted into the urine (Ae%)		7 time intervals up to Day 4. If Day 4 is not the end of the study, sample collection will continue in 24 hour intervals until discharge up to Day 9	No
Primary	Pharmacokinetics of BAL8728 (cleavage product) in urine: renal clearance (CLr)		7 time intervals up to Day 4. If Day 4 is not the end of the study, sample collection will continue in 24 hour intervals until discharge up to Day 9	No
Primary	Pharmacokinetics of BAL4815 (isavuconazole) in plasma: AUClast		20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9	No
Primary	Pharmacokinetics of BAL4815 (isavuconazole) in plasma: Cmax		20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9	No
Primary	Pharmacokinetics of BAL4815 (isavuconazole) in plasma: tmax		20 time points up to Day 4. If Day 4 is not the end of the study, samples will be drawn once a day up to Day 9	No
Secondary	Metabolic profile of BAL8728 and possible metabolites in plasma, urine, and feces		Up to 3 days (72 hours) after dosing	No